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  • 标题:PHF2 histone demethylase prevents DNA damage and genome instability by controlling cell cycle progression of neural progenitors
  • 本地全文:下载
  • 作者:Stella Pappa ; Stella Pappa ; Natalia Padilla
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2019
  • 卷号:116
  • 期号:39
  • 页码:19464-19473
  • DOI:10.1073/pnas.1903188116
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Histone H3 lysine 9 methylation (H3K9me) is essential for cellular homeostasis; however, its contribution to development is not well established. Here, we demonstrate that the H3K9me2 demethylase PHF2 is essential for neural progenitor proliferation in vitro and for early neurogenesis in the chicken spinal cord. Using genome-wide analyses and biochemical assays we show that PHF2 controls the expression of critical cell cycle progression genes, particularly those related to DNA replication, by keeping low levels of H3K9me3 at promoters. Accordingly, PHF2 depletion induces R-loop accumulation that leads to extensive DNA damage and cell cycle arrest. These data reveal a role of PHF2 as a guarantor of genome stability that allows proper expansion of neural progenitors during development..
  • 关键词:histone demethylation ; chromatin transcription ; neuronal progenitor proliferation ; PHF2
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